Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/96190
Title:
Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.
Authors:
Whetton, Anthony D; Heyworth, Clare M; Nicholls, S E; Evans, C A; Lord, J M; Dexter, T Michael; Owen-Lynch, P J
Abstract:
Granulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.
Affiliation:
Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.
Citation:
Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells. 1994, 125 (3):651-9 J. Cell Biol.
Journal:
The Journal of Cell Biology
Issue Date:
May-1994
URI:
http://hdl.handle.net/10541/96190
PubMed ID:
7513707
Type:
Article
Language:
en
ISSN:
0021-9525
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWhetton, Anthony Den
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorNicholls, S Een
dc.contributor.authorEvans, C Aen
dc.contributor.authorLord, J Men
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorOwen-Lynch, P Jen
dc.date.accessioned2010-04-09T13:56:25Z-
dc.date.available2010-04-09T13:56:25Z-
dc.date.issued1994-05-
dc.identifier.citationCytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells. 1994, 125 (3):651-9 J. Cell Biol.en
dc.identifier.issn0021-9525-
dc.identifier.pmid7513707-
dc.identifier.urihttp://hdl.handle.net/10541/96190-
dc.description.abstractGranulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Cell Growth Factorsen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshCell Separation-
dc.subject.meshCells, Cultured-
dc.subject.meshDiglycerides-
dc.subject.meshEnzyme Activation-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Cell Growth Factors-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshInositol Phosphates-
dc.subject.meshMacrophage Colony-Stimulating Factor-
dc.subject.meshMacrophages-
dc.subject.meshMice-
dc.subject.meshNeutrophils-
dc.subject.meshProtein Kinase C-
dc.subject.meshSecond Messenger Systems-
dc.subject.meshStem Cell Factor-
dc.titleCytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.en
dc.identifier.journalThe Journal of Cell Biologyen
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